Improving the bioavailability and therapeutic efficacy of felodipine for the control of diabetes-associated atherosclerosis: In vitro and in vivo characterization.

Felodipine has proven to be effective as an atherosclerosis therapy because it increases blood flow to the vessel wall. However, the poor solubility, low bioavailability, and hepatic first-pass metabolism of oral felodipine compromise its therapeutic effectiveness. The study's goal is to create a nasal pH-sensitive hydrogel of felodipine-loaded invasomes (IPHFI) that will improve felodipine's release, permeation, bioavailability, and efficacy as a potential diabetes-associated atherosclerosis therapy. According to the pre-formulation study, the felodipine-loaded invasomes formulation composed of phospholipid (3%w/v), cholesterol (0.16%w/v), ethanol (3%v/v) and cineole (1%v/v) was chosen as the optimum formulation. The optimum formulation was characterized in vitro and then mixed with a mixture of chitosan and glyceryl monooleate to make the IPHFI formulation. The IPHFI formulation enhanced the release and permeation of felodipine by 2.99 and 3-fold, respectively. To assess the efficacy and bioavailability of the IPHFI formulation, it was studied in vivo using an experimental atherosclerosis rat model. Compared to oral free felodipine, the nasal administration of the IPHFI formulation increased the bioavailability by 3.37-fold and decreased the serum cholesterol, triglycerides, LDL, and calcification score by 1.56, 1.53, 1.80, and 1.18 ratios, respectively. Thus, nasal IPHFI formulation may represent a promising diabetes-associated atherosclerosis therapy.

Neuro-modulatory impact of felodipine against experimentally-induced Parkinson's disease: Possible contribution of PINK1-Parkin mitophagy pathway.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, characterized by motor and psychological dysfunction. Palliative treatment and dopamine replenishment therapy are the only available therapeutic options. Calcium channel blockers (CCBs) have been reported to protect against several neurodegenerative disorders. The current study was designed to evaluate the neuroprotective impact of Felodipine (10 mg/kg, orally) as a CCB on motor and biochemical dysfunction associated with experimentally induced PD using rotenone (2.5 mg/kg, IP) and to investigate the underlying mechanisms. Rotenone induced deleterious neuromotor outcomes, typical of those associated with PD. The striatum revealed increased oxidative burden and NO levels with decreased antioxidant capacity. Nrf2 content significantly decreased with the accumulation of α-synuclein and tau proteins in both the substantia nigra and striatum. These observations significantly improved with felodipine treatment. Of note, felodipine increased dopamine levels in the substantia nigra and striatum as confirmed by the suppression of inflammation and the significant reduction in striatal NF-κB and TNF-α contents. Moreover, felodipine enhanced mitophagy, as confirmed by a significant increase in mitochondrial Parkin and suppression of LC3a/b and SQSTM1/p62. In conclusion, felodipine restored dopamine synthesis, attenuated oxidative stress, inflammation, and mitochondrial dysfunction, and improved the mitophagy process resulting in improved PD-associated motor impairment.

Threading the needle: Achieving simplicity and performance in cellulose alkanoate ω-carboxyalkanoates for amorphous solid dispersion.

Most active pharmaceutical ingredients (APIs) suffer from poor water solubility, often keeping them from reaching patients. To overcome the issues of poor drug solubility and subsequent low bioavailability, amorphous solid dispersions (ASDs) have garnered much attention. Cellulose ester derivatives are of interest for ASD applications as they are benign, sustainable-based, and successful in commercial drug delivery systems, e.g. in osmotic pump systems and as commercial ASD polymers. Synthesis of carboxy-pendant cellulose esters is a challenge, due in part to competing reactions between carboxyls and hydroxyls, forming ester crosslinks. Herein we demonstrate proof-of-concept for a scalable synthetic route to simple, yet highly promising ASD polymers by esterifying cellulose polymers through ring-opening of cyclic succinic or glutaric anhydride. We describe the complexity of such ring-opening reactions, not previously well-described, and report ways to avoid gelation. We report synthesis, characterization, and preliminary in vitro ASD evaluations of fifteen such derivatives. Synthetic routes were designed to accommodate these criteria: no protecting groups, no metal catalysts, mild conditions with standard reagents, simple purification, and one-pot synthesis. Finally, these designed ASD polymers included members that maintained fast-crystallizing felodipine in solution and release it from an ASD at rather high 20 % drug loading (DL).

In vitro models for neuropathic pain phenotypic screening in brain therapeutics.

The discovery of brain therapeutics faces a significant challenge due to the low translatability of preclinical results into clinical success. To address this gap, several efforts have been made to obtain more translatable neuronal models for phenotypic screening. These models allow the selection of active compounds without predetermined knowledge of drug targets. In this review, we present an overview of various existing models within the field, examining their strengths and limitations, particularly in the context of neuropathic pain research. We illustrate the usefulness of these models through a comparative review in three crucial areas: i) the development of novel phenotypic screening strategies specifically for neuropathic pain, ii) the validation of the models for both primary and secondary screening assays, and iii) the use of the models in target deconvolution processes.

The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC.

This study aimed to explore the role and mechanism of felodipine in lung cancer therapy. Murine subcutaneous lung squamous cancer (LUSC) models constructed by KLN-205 cells were utilized to assess the effect of felodipine monotherapy and in combination with the programmed cell death protein 1 antibody (PD1ab) and cytotoxic T lymphocyte-associated antigen-4 (CTLA4ab). Immunohistochemistry analysis was subsequently applied to detect the number of CD8+ T cells and Ki67+ cells. Lastly, a series of in vitro and in vivo experiments were performed to evaluate the effects of felodipine on human LUSC cells and explore the preliminary mechanism underlying felodipine inhibition. The results revealed that felodipine monotherapy exerted a significant inhibitory effect on LUSC growth and synergistic antitumoral activity with PD1ab and CTLA4ab. Meanwhile, immunohistochemistry analysis displayed that felodipine promoted CD8+ T-cell infiltration and downregulated Ki67 expression in tumor cells. Moreover, in vitro and in vivo experiments utilizing human LUSC cells determined that felodipine impaired the proliferative and migratory abilities of cancer cells. In addition, TCGA data analysis uncovered that nuclear factor of activated T cell (NFAT1) expression was positively correlated with overall survival and disease-free survival. Finally, the cell counting kit-8 assay signaled that felodipine might suppress tumor growth by modulating NFAT1.

Effect of felodipine on indomethacin-induced gastric ulcers in rats.

Felodipine is a calcium channel blocker with antioxidant and anti-inflammatory properties. Researchers have stated that oxidative stress and inflammation also play a role in the pathophysiology of gastric ulcers caused by nonsteroidal anti-inflammatory drugs. The aim of this study was to investigate the antiulcer effect of felodipine on indomethacin-induced gastric ulcers in Wistar rats and compare it with that of famotidine. The antiulcer activities of felodipine (5 mg/kg) and famotidine were investigated biochemically and macroscopically in animals treated with felodipine (5 mg/kg) and famotidine in combination with indomethacin. The results were compared with those of the healthy control group and the group administered indomethacin alone. It was observed that felodipine suppressed the indomethacin-induced malondialdehyde increase (P<0.001); reduced the decrease in total glutathione amount (P<0.001), reduced the decrease superoxide dismutase (P<0.001), and catalase activities (P<0.001); and significantly inhibited ulcers (P<0.001) at the tested dose compared with indomethacin alone. Felodipine at a dose of 5 mg/kg reduced the indomethacin-induced decrease in cyclooxygenase-1 activity (P<0.001) but did not cause a significant reduction in the decrease in cyclooxygenase-2 activity. The antiulcer efficacy of felodipine was demonstrated in this experimental model. These data suggest that felodipine may be useful in the treatment of nonsteroidal anti-inflammatory drug-induced gastric injury.

Structure-activity relationship of dihydropyridines for rhabdomyosarcoma.

Childhood muscle-related cancer rhabdomyosarcoma is a rare disease with a 50-year unmet clinical need for the patients presented with advanced disease. The rarity of ∼350 cases per year in North America generally diminishes the viability of large-scale, pharmaceutical industry driven drug development efforts for rhabdomyosarcoma. In this study, we performed a large-scale screen of 640,000 compounds to identify the dihydropyridine (DHP) class of anti-hypertensives as a priority compound hit. A structure-activity relationship was uncovered with increasing cell growth inhibition as side chain length increases at the ortho and para positions of the parent DHP molecule. Growth inhibition was consistent across n = 21 rhabdomyosarcoma cell line models. Anti-tumor activity in vitro was paralleled by studies in vivo. The unexpected finding was that the action of DHPs appears to be other than on the DHP receptor (i.e., L-type voltage-gated calcium channel). These findings provide the basis of a medicinal chemistry program to develop dihydropyridine derivatives that retain anti-rhabdomyosarcoma activity without anti-hypertensive effects.

Practical Synthesis of 1,4-Dihydropyridines on Heterogeneous Sulfonicmodified Silica (SBA-15-SO3H) Catalyst Under Mild Condition.

AIMS: Synthesis of 1,4-Dihydropyridines (1,4-DHP) using heterogeneous catalyst under mild condition. OBJECTIVE: Our objective is to explore new applications of non-metal heterogeneous catalysts in the synthesis of 1,4-DHP derivatives in a greener and more efficient approach. METHODS: A greener and more efficient method for the synthesis of 1,4-DHPs and an asymmetric 1,4-DHP (Felodipine drug) was successfully developed in high yields using a heterogeneous SBA- 15-SO3H catalyst. RESULTS: A series of symmetric 1,4-DHP and an asymmetric 1,4-DHP (Felodipine drug) were successfully prepared in high yields using a heterogeneous SBA-15-SO3H catalyst. CONCLUSION: The catalyst, SBA-15-SO3H, exhibited an efficient catalyst activity for the synthesis of 1,4-DHP derivatives in high yields from the aldehyde, ß-ketoester, and NH4OAc as a nitrogen source under mild conditions and short reaction time. Bronsted acid sites of this solid catalyst were figured out to play a key role in this transformation. Interestingly, our catalyst is air-stable and can be recycled at least 5 times without losing catalytic activity.

Enhancement of the Solubility of BS Class II Drugs with MOF and MOF/GO Composite Materials: Case Studies of Felodipine, Ketoprofen and Ibuprofen.

In this research, a novel composite material composed of Metal-Organic Framework material (MOF) and graphite oxide was synthesized and evaluated as a possible drug-loading vehicle. HKUST-1, a MOF material originally designed by the Hong Kong University of Science and Technology, was used as a model porous material. The aim was to synthesize a drug delivery vehicle for modifying the release kinetics and solubility of poorly soluble drugs (BSC Class II drugs); these are drugs that are known to have poor bioavailability due to their low solubility. We used ketoprofen, ibuprofen, and felodipine as models for BSC Class II drugs. The drugs were loaded onto composite materials through adsorption. The adsorption of these three drugs into the matrix of HKUST-1/GO (graphite oxide), HKUST-1, and graphite oxide was compared. The loading efficiency of the drugs onto the carrier was dependent on the drug molecule and the composition of the drug carrier. The inclusion of graphite oxide in the drug carrier matrix improved the drug loading capacity and modified the drug release rate. The loading of the three drugs felodipine, ketoprofen, and ibuprofen onto HKUST-1 were 33.7, 58, and 79 mg/g respectively. The incorporation of GO into the HKUST-1 matrix resulted in an increase in the loading by 16 and 4 mg/g for the ketoprofen and ibuprofen drugs. When compared to the pure drugs, the solubility of all three drugs in the HKUST-1/GO matrix increased by at least 6 folds.

Structure Determination of Felodipine Photoproducts in UV-Irradiated Medicines Using ESI-LC/MS/MS.

Dihydropyridine drugs are well known as photodegradable pharmaceuticals. Herein, we evaluate the photostability of felodipine (FL) medicine (Splendil® (SPL) tablets) and its altered forms (powders and suspensions). FL is a type of dihydropyridine drug, but its photochemical behavior is unknown. FL contents after ultraviolet light (UV) irradiation for 24 h were monitored using high-performance liquid chromatography (HPLC). Values of the residual amounts of FL in UV-irradiated SPL powders and suspensions were 32.76 ± 4.88% and 0.79 ± 0.74%, respectively, with the generation of two photoproducts (FL photoproduct 1 and 2). To identify the chemical structures of these photoproducts, electrospray ionization liquid chromatography mass spectrometry (ESI-LC/MS/MS) analysis was performed. Based on their mass-to-charge ratio values and fragment patterns, it was proposed that FL photoproduct 1 was a pyridine derivative and FL photoproduct 2 was an FL dimer. Interestingly, generation rates of FL photoproduct 1 and 2 were dependent on the presence of the aqueous media. The photodimerization of FL was induced in UV-irradiated SPL suspensions. This is the first report evaluating the photostability of SPL tablets and its altered forms and estimating FL photoproducts induced by UV irradiation in the formulation of SPL.

Lipid-Polymer Hybrid Nanocarriers for Oral Delivery of Felodipine: Formulation, Characterization and Ex Vivo Evaluation.

Purpose: Felodipine, is a calcium-channel antagonist used for hypertension and angina pectoris. It is practically insoluble in aqueous media and shows low oral bioavailability (15%-20%). This investigation aims to prepare and characterize oral felodipine lipid-polymer hybrid nanocarriers (LPHNs) to increase solubility and control delivery for increasing bioavailability and enhance patient compliance. Methods: The newly microwave-based method was prepared with felodipine LPHNs (H1-H35) successfully. The (H1-H35) were subjected to thermodynamic stability experiments. After that, select nine felodipine LPHNs (F1-F9) that have smart physical stability for further optimization of different characterization processes. Results: The felodipine LPHNs (F4) are considered the most optimized formula. It was characterized by lower particle size (33.3 nm), lower PDI (0.314), high zeta potential (13.6 mV), entrapment efficiency is (81.645% w/w), drug loading is (16.329% w/w), the pH value is 4, excellent percent of light transmittance (95.5%), pseudoplastic rheogram, significantly high (P < 0.05) dissolution rate with sustained drug delivery and success ex-vivo intestinal permeation attributes. The (F4) subject for further investigations of Fourier transformed infrared spectroscopy (FTIR), atomic force microscopy (AFM), and transmission electron microscopy (TEM). The results of FTIR, AFM, and TEM indicate there is no interaction between the felodipine and excipients and that the particulate system in the nanoscale dispersion system confirms the high stability. Conclusion: The optimized felodipine LPHNs (F1-F9) formulations were smart formulations for sustained oral delivery of felodipine and that F4 was the most optimized formula according to its characterization processes.

L-Type Ca2+ Channel Inhibition Rescues the LPS-Induced Neuroinflammatory Response and Impairments in Spatial Memory and Dendritic Spine Formation.

Ca2+ signaling is implicated in the transition between microglial surveillance and activation. Several L-type Ca2+ channel blockers (CCBs) have been shown to ameliorate neuroinflammation by modulating microglial activity. In this study, we examined the effects of the L-type CCB felodipine on LPS-mediated proinflammatory responses. We found that felodipine treatment significantly diminished LPS-evoked proinflammatory cytokine levels in BV2 microglial cells in an L-type Ca2+ channel-dependent manner. In addition, felodipine leads to the inhibition of TLR4/AKT/STAT3 signaling in BV2 microglial cells. We further examined the effects of felodipine on LPS-stimulated neuroinflammation in vivo and found that daily administration (3 or 7 days, i.p.) significantly reduced LPS-mediated gliosis and COX-2 and IL-1ß levels in C57BL/6 (wild-type) mice. Moreover, felodipine administration significantly reduced chronic neuroinflammation-induced spatial memory impairment, dendritic spine number, and microgliosis in C57BL/6 mice. Taken together, our results suggest that the L-type CCB felodipine could be repurposed for the treatment of neuroinflammation/cognitive function-associated diseases.

"Novel mucoadhesive PLGA-PVM/MA micro-nanocomposites loaded with felodipine intended for pulmonary administration by nebulization".

Poly(latic-co-glycolic) acid (PLGA) nanoparticles loaded with felodipine (FEL) were embedded in a mucoadhesive matrix of poly (methyl vinyl ether-co-maleic anhydride) (PVM/MA) to prepare micro-nanoparticulate composites by particle engineering. Composites were characterized for physical and rheological properties and formulated with inhalable grade lactose. In-vitro characterization studies such as drug release kinetics, and mucoadhesive, and aerodynamic properties were performed. The in-vivo efficacy was evaluated by administering the optimized composites by nebulization in hypertensive rats. The obtained FEL-PLGA-PVM/MA composites of 1,069 ± 82 nm showed sustained drug release and mucoadhesive properties. Bulk and tapped densities of composites mixed with lactose were 0.08-0.13 g/mL and 0.18-0.30 g/mL, respectively, with mass median aerodynamic diameters (MMAD) in a range of 1.29-12.0 µm. After pulmonary administration of the composites, a decrease in systolic and diastolic blood pressure was observed within the first 3 h, of -9.0 ± 1.3 % and -13.9 ± 3.3 %, respectively, with a maximal effect at 12 h (sustained during 144 h), in contrast to pure FEL, which showed no significant decrease in blood pressure (1.6 ± 2.7 % and 4.1 ± 4.1 %). Findings suggest that novel mucoadhesive FEL-PLGA-PVM/MA composites are a promising strategy formulation to treat systemic diseases by pulmonary route.

A Physiologically Based Pharmacokinetic and Pharmacodynamic Model of the CYP3A4 Substrate Felodipine for Drug-Drug Interaction Modeling.

The antihypertensive felodipine is a calcium channel blocker of the dihydropyridine type, and its pharmacodynamic effect directly correlates with its plasma concentration. As a sensitive substrate of cytochrome P450 (CYP) 3A4 with high first-pass metabolism, felodipine shows low oral bioavailability and is susceptible to drug-drug interactions (DDIs) with CYP3A4 perpetrators. This study aimed to develop a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) parent-metabolite model of felodipine and its metabolite dehydrofelodipine for DDI predictions. The model was developed in PK-Sim® and MoBi® using 49 clinical studies (94 plasma concentration-time profiles in total) that investigated different doses (1-40 mg) of the intravenous and oral administration of felodipine. The final model describes the metabolism of felodipine to dehydrofelodipine by CYP3A4, sufficiently capturing the first-pass metabolism and the subsequent metabolism of dehydrofelodipine by CYP3A4. Diastolic blood pressure and heart rate PD models were included, using an Emax function to describe the felodipine concentration-effect relationship. The model was tested in DDI predictions with itraconazole, erythromycin, carbamazepine, and phenytoin as CYP3A4 perpetrators, with all predicted DDI AUClast and Cmax ratios within two-fold of the observed values. The model will be freely available in the Open Systems Pharmacology model repository and can be applied in DDI predictions as a CYP3A4 victim drug.

Small scale in vitro method to determine a potential bioequivalent equilibrium solubility range for fed human intestinal fluid.

Intestinal drug solubility is a key parameter controlling oral absorption but varies both intra and inter individuals and between the fasted and fed states, with food intake known to alter the bioavailability of many compounds. Intestinal solubility can be measured in vitro either using sampled fed human intestinal fluid (FeHIF) or simulated fed intestinal fluid (SIF) but neither approach is optimal. FeHIF is difficult to obtain and variable, whilst for fed SIF multiple recipes are available with no consensus on the ideal version. A recent study characterised FeHIF aspirates using a multidimensional approach and calculated nine simulated media recipes that covered over ninety percent of FeHIF compositional variability. In this study the equilibrium solubility of thirteen drugs have been measured using the nine simulated media recipes and compared to multiple previous design of experiment (DoE) studies, which have examined the impact of fed SIF media components on solubility. The measured nine media solubility data set is only statistically equivalent to the large scale 92 media DoE in 4 out of 13 drug comparisons, but has improved equivalence against small scale DoEs (9 or 10 media) with 6 out of 9 or 10 out of 12 (9 and 10 media respectively) equivalent. Selective removal of non-biorelevant compositions from the 92 media DoE improves statistical equivalence to 9 out of 13 comparisons. The results indicate that solubility equivalence is linked to media component concentrations and compositions, the nine media system is measuring a similar solubility space to previous systems, with a narrower solubility range than the 92 point DoE but equivalent to smaller DoE systems. Phenytoin and tadalafil display a narrow solubility range, a behaviour consistent with previous studies in fed and fasted states and only revealed through the multiple media approach. Custom DoE analysis of the nine media results to determine the most statistically significant component influencing solubility does not detect significant components. Indicating that the approach has a low statistical resolution and is not appropriate if determination of media component significance is required. This study demonstrates that it is possible to assess the fed intestinal equilibrium solubility envelope using the nine media recipes obtained from a multi-dimensional analysis of fed HIF. The derivation of the nine media compositions coupled with the results in this study indicate that the solubility results are more likely to reflect the fed intestinal solubility envelope than previous DoE studies and highlight that the system is worthy of further investigation.

Felodipine Determination by a CdTe Quantum Dot-Based Fluorescent Probe.

In this work, a CdTe quantum dot-based fluorescent probe was synthesized to determine felodipine (FEL). The synthesis conditions, structure, and interaction conditions with FEL of CdTe quantum dots were analysed by fluorescence spectrophotometry, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), UV-visible spectroscopy, and TEM. The CdTe QD concentration was 2.0 × 10-4 mol/L. The amount of quantum dots controlled in the experiment was 0.8 mL. The controlled feeding ratio of N (Cd2+):N (Te2-):N (TGA) was 2:1:4, the heating temperature was 140 °C, the heating time was 60 min, and the pH of the QD precursor was adjusted to 11 for subsequent experiments. The UV-visible spectrum showed that the emission wavelength of CdTe quantum dots at 545 nm was the strongest and symmetric. The particle size of the synthesized quantum dots was approximately 5 nm. In the interaction of CdTe quantum dots with FEL, the FEL dosage was 1.0 mL, the optimal pH value of Tris-HCl buffer was 8.2, the amount of buffer was 1.5 mL, and the reaction time was 20 min. The standard curve of FEL was determined under the optimal synthesis conditions of CdTe quantum dots and reaction of CdTe quantum dots with FEL. The linear equation was Y = 3.9448x + 50.068, the correlation coefficient R2 was 0.9986, and the linear range was 5 × 10-6-1.1 × 10-4 mol/L. A CdTe quantum dot-based fluorescent probe was successfully constructed and could be used to determine the FEL tablet content.

Development of Simple Dissolution Methods for Felodipine and Combined Amlodipine Besylate-Indapamide Extended Release Tablets without Stationary (Felodipine) Basket.

BACKGROUND: The dissolution method for certain drugs needs specialized conditions. Dissolution testing for felodipine extended release (ER) tablets (Plendil® 5 mg) and amlodipine-indapamide fixed dose (Natrilam®, 5/1.5 mg) ER tablets requires the use of a stationary (felodipine) basket in USP Apparatus II. OBJECTIVE: The study aimed to develop simple methods for Plendil® and Natrilam® without the use of a felodipine basket. METHODS: The dissolution profiles obtained from different media and paddle speeds were used to compute miscellaneous dissolution parameters and were compared to those obtained from standard (existing) methods using a felodipine basket. RESULTS: The f1, f2, and bootstrap f2 (5th % percentile) values for Plendil® 2.47, 88.17, and 54.62, respectively, and all other dissolution factors revealed similarity between standard and the selected test method with 1% Tween 20 at 50 rpm. For Natrilam®, f1 and f2 and bootstrap f2 5.13, 72.92, and 62.67, respectively, and all other dissolution parameters showed similarity of the standard and selected test method using 0.1N HCl media having 0.38 gm/L EDTA with a sinker at 100 rpm. Release of products assumed zero-order and Weibull model, respectively. CONCLUSION: Test dissolution methods for Plendil® and Natrilam® tablets produced equivalent dissolution profiles compared to their respective standard methods with stationary basket USP Apparatus II.

Oral Rehabilitation of a Patient With Generalized Inflammatory Gingival Overgrowth Exacerbated by Felodipine: A Case Report.

Gingival enlargement may manifest as a side effect of medications (calcium channel blockers, anticonvulsants, or immunosuppressants) and may be associated with inflammation, malignancy, or genetic inheritance. This condition has a significant impact on a patient's quality of life and affects their oral health status. This case report describes the management of a 68-year-old gentleman who presented with generalized gingival enlargement and chronic periapical abscess originating from tooth 34, which served as an abutment for a fixed partial prosthesis. The patient's medical history revealed that felodipine, an antihypertensive medication, was prescribed to him. A comprehensive treatment plan was developed to improve the patient's quality of life.

The Physical Stability of Felodipine and Its Recrystallization from an Amorphous Solid Dispersion Studied by NMR Relaxometry.

The 1H nuclear magnetic resonance (NMR) relaxometry method was applied to investigate the physical stability of an active pharmaceutical ingredient (API) and, for the first time, its recrystallization process in an amorphous solid dispersion system (ASD). The ASD of felodipine and polyvinylpyrrolidone (PVP) was prepared using the solvent evaporation method in a mass ratio of 50:50. In the first stage of the study (250 days), the sample was stored at 0% relative humidity (RH). The recovery of magnetization was described by one-exponential function. In the second stage (300 days in 75% relative humidity), the recrystallization process of felodipine was studied, showing in the sample three components of equilibrium magnetization related to (i) crystalline felodipine, (ii) water, and (iii) felodipine and PVP remaining in the ASD. The study shows that the 1H NMR relaxometry method is a very useful tool for analysing the composition of a three-phase system mixed at the molecular level and for the investigation of recrystallization process of API in amorphous solid dispersion system.